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https://www.readbyqxmd.com/read/28929293/predictive-biomarkers-for-asthma-therapy
#1
REVIEW
Sarah K Medrek, Amit D Parulekar, Nicola A Hanania
PURPOSE OF REVIEW: Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. RECENT FINDINGS: Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment...
September 19, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28921447/structure-pharmacology-and-roles-in-physiology-of-the-p2y12-receptor
#2
Ivar von Kügelgen
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel block P2Y12 receptors and, thereby, inhibit ADP-induced platelet aggregation...
September 12, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921377/basophils-activated-via-tlr-signaling-may-contribute-to-pathophysiology-of-type-1-autoimmune-pancreatitis
#3
Masato Yanagawa, Kazushige Uchida, Yugo Ando, Takashi Tomiyama, Takashi Yamaguchi, Tsukasa Ikeura, Toshiro Fukui, Akiyoshi Nishio, Yoshiko Uemura, Takayuki Miyara, Hiroyuki Okamoto, Souhei Satoi, Kazuichi Okazaki
BACKGROUND: Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP. METHODS: By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells...
September 18, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28919369/effect-of-airway-remodeling-and-hyperresponsiveness-on-complexity-of-breathing-pattern-in-rat
#4
Mehdi Eslami-Behroozi, Mohammad Javan, Mohammad Reza Raoufy
The complexity of respiratory dynamics is decreased, in association with disease severity, in patients with asthma. However, the pathophysiological basis of decreased complexity of breathing pattern in asthma is not clear. In the present study, we investigated the effect of airway remodeling and hyperresponsiveness induced by repeated bronchoconstriction (using methacholine) on breathing pattern in rats with or without allergen-induced sensitization. Entropy analysis of respiratory variability showed decreased irregularity (less complexity) of respiratory rhythm in this rat model of asthma...
September 15, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28892548/pediatric-obstructive-sleep-apnea-and-asthma-clinical-implications
#5
Michelle Trivedi, Mai El Mallah, Evan Bailey, Ted Kremer, Lawrence M Rhein
Obstructive sleep apnea (OSA) and asthma are common conditions in children with preventable long-term consequences. There is significant overlap in symptomatology and pathophysiology for pediatric OSA and asthma. Recent evidence supports clear associations between the two diseases; however, causality has not been demonstrated. Regardless, it is important to recognize the overlap and evaluate for the other condition when one is present. For example, in patients with severe OSA, clinical evaluation for asthma should be considered, including history for typical asthma symptoms and spirometry...
September 1, 2017: Pediatric Annals
https://www.readbyqxmd.com/read/28879503/asthma-phenotypes-and-endotypes-implications-for-personalised-therapy
#6
Katrina Dean, Robert Niven
Asthma is increasingly recognised as a heterogeneous group of diseases with similar clinical presentations rather than a singular disease entity. Asthma was historically categorised by clinical symptoms; however, newer methods of subgrouping, describing and categorising the disease have sub-defined asthma. These sub-definitions are intermittently called phenotypes or endotypes, but the real meanings of these words are poorly understood. Novel treatments are currently and increasingly available, partly in the monoclonal antibody environment, and also some physical therapies (bronchial thermoplasty), but additionally small molecules are not far away from clinical practice...
September 6, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28868030/association-of-posterior-reversible-encephalopathy-syndrome-and-transient-apical-ballooning-syndrome-takotsubo-first-case-report-of-a-man-and-review-of-the-literature
#7
Stephan Grimaldi, Emilie Doche, Caroline Rey, Nadia Laksiri, Salah Boussen, Jacques Quilici, Emmanuelle Robinet, Fabien Devemy, Jean Pelletier
INTRODUCTION: An association of posterior reversible encephalopathy syndrome (PRES) and takotsubo is rare. We present the first case of a male patient. CASE REPORT: A 69-year-old man presented to the hospital in a persistent comatose state following a generalized tonic-clonic seizure with high blood pressure. The electrocardiogram revealed transient left bundle branch block. Troponin and BNP were elevated. Cardiac ultrasound showed large apical akinesia with altered left ventricular ejection fraction, and the left ventriculogram showed characteristic regional wall motion abnormalities involving the mid and apical segments...
May 2017: Case Reports in Neurology
https://www.readbyqxmd.com/read/28865412/association-between-4259-t-g-and-574-g-t-polymorphisms-of-tim-3-with-asthma-in-an-iranian-population
#8
Maryam Sadri, Mazdak Ganjalikhani-Hakemi, Peyman Akbari, Rasoul Salehi, Sedighe Rastaghi, Ramin Ghasemi, Rezvan Meshkat
T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR)...
August 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28855694/functional-autoantibodies-targeting-g-protein-coupled-receptors-in-rheumatic-diseases
#9
REVIEW
Otavio Cabral-Marques, Gabriela Riemekasten
G protein-coupled receptors (GPCRs) comprise the largest and most diverse family of integral membrane proteins that participate in different physiological processes such as the regulation of the nervous and immune systems. Besides the endogenous ligands of GPCRs, functional autoantibodies are also able to bind GPCRs to trigger or block intracellular signalling pathways, resulting in agonistic or antagonistic effects, respectively. In this Review, the effects of functional GPCR-targeting autoantibodies on the pathogenesis of autoimmune diseases, including rheumatic diseases, are discussed...
August 31, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28840844/increased-serum-il-17a-and-th2-cytokine-levels-in-patients-with-severe-uncontrolled-asthma
#10
Takehiro Hasegawa, Hitoshi Uga, Akio Mori, Hirokazu Kurata
Asthma is a syndrome of chronic bronchial inflammation and airway remodelling. Initially, asthma has been categorized into atopic and nonatopic types, based on antigen-specific IgE levels. Moreover, recently, asthma has been classified into different endotypes based on its pathophysiology, leading to the selection of the most optimal and effective therapies. Although T helper cell type 2 (Th2) cytokines were proven to play critical roles in atopic asthma, IL-17A has been reported to be involved in severe refractory asthma...
March 1, 2017: European Cytokine Network
https://www.readbyqxmd.com/read/28831046/pulmonary-inflammation-and-cytokine-dynamics-of-bronchoalveolar-lavage-fluid-from-a-mouse-model-of-bronchial-asthma-during-a-h1n1-pdm09-influenza-infection
#11
Yousuke Fujimoto, Shunji Hasegawa, Takeshi Matsushige, Hiroyuki Wakiguchi, Tamaki Nakamura, Hideki Hasegawa, Noriko Nakajima, Akira Ainai, Atsunori Oga, Hiroshi Itoh, Komei Shirabe, Shoichi Toda, Ryo Atsuta, Tsuneo Morishima, Shouichi Ohga
Asthmatic patients present more rapid progression of respiratory distress after A(H1N1)pdm09 influenza infection than after seasonal infection. Here, we sought to clarify the pathophysiology of early deterioration in asthmatic patients after A(H1N1)pdm09 infection. Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. In asthma/A(H1N1)pdm09 mice, IL-6 and TNF-α levels peaked at 3 days post-infection and were higher than those in all other groups...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826280/severe-therapy-resistant-asthma-in-children-translational-approaches-to-uncover-sub-phenotypes
#12
Aldara Martin Alonso, Valentina Fainardi, Sejal Saglani
Paediatric severe therapy resistant asthma (STRA) affects a very small proportion of all children with asthma, but results in significant morbidity, has a high risk of mortality and utilises approximately half of all healthcare resources for childhood asthma. children with STRA need add-on 'beyond guidelines' therapies because of poor control despite maximal conventional treatments and optimisation of basic asthma management. however, STRA is heterogeneous with marked phenotypic variation between patients and mechanisms from adult severe asthma cannot be extrapolated to children...
August 21, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28817310/semaphorins-and-their-roles-in-airway-biology-potential-as-therapeutic-targets
#13
Hesam Movassagh, Forough Khadem, Abdelilah S Gounni
Semaphorins are a large family of proteins originally identified as axon guidance cues which play a crucial role in neural development. They are also ubiquitously expressed beyond the nervous system and contribute to regulation of essential cell functions such as cell migration, proliferation, and adhesion. Binding of semaphorins to their receptors, including plexins and neuropilins, triggers diverse signaling pathways which are involved in the pathogenesis of various diseases from cancer to autoimmune and allergic disorders...
August 17, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28810589/phenotypic-switch-in-lung-interstitial-macrophage-polarization-in-an-ovalbumin-induced-mouse-model-of-asthma
#14
Hanxiang Nie, Ailing Wang, Qing He, Qiaoyu Yang, Linlin Liu, Guqin Zhang, Yi Huang, Xuhong Ding, Hongying Yu, Suping Hu
Macrophage phenotype and function varies according to their polarized state, which in turn is dependent on microenvironmental stimuli. Under normal physiological conditions, lung interstitial macrophages that express interleukin (IL)-10 are considered to serve regulatory roles in the prevention of allergic reactions in the airways. However, the phenotypic profile of lung interstitial macrophages during the pathophysiology of asthma remains unknown. In the current study, the phenotypic characteristics of lung interstitial macrophages were investigated in an ovalbumin (OVA)-induced mouse model of asthma...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809842/noninvasive-sampling-of-mucosal-lining-fluid-for-the-quantification-of-in-vivo-upper-airway-immune-mediator-levels
#15
Helene M Wolsk, Bo L Chawes, Jonathan Thorsen, Jakob Stokholm, Klaus Bønnelykke, Susanne Brix, Hans Bisgaard
This protocol describes noninvasive sampling of undisturbed upper airway mucosal lining fluid. It also details the extraction procedure used prior to the analysis of immune mediators in fluid eluates for the study of the airway topical immune signature, without the need for stimulation procedures (often used by other techniques). The mucosal lining fluid is sampled on a strip of filter paper placed at the anterior part of the inferior turbinate and left for 2 min of absorption. Analytes are eluted from the filter papers, and the extracted protein-based eluates are analyzed by an electrochemiluminescence-based immunoassay, allowing for the high-sensitivity quantification of low- and high-level analytes in the same sample...
August 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28808576/-awake-ecco2r-superseded-intubation-in-a-near-fatal-asthma-attack
#16
Thomas-Michael Schneider, Tibor Bence, Franz Brettner
BACKGROUND: Near-fatal asthma attacks are life threatening events that often require mechanical ventilation. Extracorporeal carbon dioxide removal (ECCO2R) is, beside extracorporeal membrane oxygenation (ECMO), a well-established rescue option whenever ventilation gets to its limits. But there seems to be very rare experience with those techniques in avoiding mechanical ventilation in severe asthma attacks. CASE PRESENTATION: A 67-year-old man with a near-fatal asthma attack deteriorated under non-invasive ventilation conditions...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28802471/integrative-medicine-for-respiratory-conditions-asthma-and-chronic-obstructive-pulmonary-disease
#17
REVIEW
Gloria Y Yeh, Randy Horwitz
Asthma and chronic obstructive pulmonary disease are 2 common chronic respiratory disorders in primary care that cause considerable morbidity and mortality. This article reviews disease pathophysiology and outlines an integrative, multidimensional approach to the evaluation and management of these conditions, including pharmacotreatment, nutrition, supplements, self-care strategies, mind-body therapies, and other integrative modalities.
September 2017: Medical Clinics of North America
https://www.readbyqxmd.com/read/28792151/physical-activity-sedentary-habits-sleep-and-obesity-are-associated-with-asthma-allergic-rhinitis-and-atopic-dermatitis-in-korean-adolescents
#18
Man Sup Lim, Chang Hee Lee, Songyong Sim, Sung Kwang Hong, Hyo Geun Choi
PURPOSE: Since pathophysiologic evidence has been raised to suggest that obesity could facilitate an allergic reaction, obesity has been known as an independent risk factor for allergic disease such as asthma. However, the relationship between sedentary behavior and lifestyle which could lead to obesity, and those allergic diseases remains unclear. MATERIALS AND METHODS: We analyzed the relations between physical activity, including sitting time for study, sitting time for leisure and sleep time, and obesity, asthma, allergic rhinitis, and atopic dermatitis using the Korea Youth Risk Behavior Web-based Survey, which was conducted in 2013...
September 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28769820/inhibition-of-toll-like-receptor-signaling-as-a-promising-therapy-for-inflammatory-diseases-a-journey-from-molecular-to-nano-therapeutics
#19
REVIEW
Wei Gao, Ye Xiong, Qiang Li, Hong Yang
The recognition of invading pathogens and endogenous molecules from damaged tissues by toll-like receptors (TLRs) triggers protective self-defense mechanisms. However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma. Therefore, inhibitors/antagonists targeting TLR signals may be beneficial to treat these disorders...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28757156/emerging-understanding-of-the-mechanism-of-action-of-bronchial-thermoplasty-in-asthma
#20
REVIEW
J N S d'Hooghe, N H T Ten Hacken, E J M Weersink, P J Sterk, J T Annema, P I Bonta
Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate-to-severe asthma patients who are uncontrolled despite optimal medical therapy. Effectiveness of BT has been demonstrated in several randomized clinical trials. However, the asthma phenotype that benefits most of this treatment is unclear, partly because the mechanism of action is incompletely understood. BT was designed to reduce the amount of airway smooth muscle (ASM), but additional direct and indirect effects on airway pathophysiology are expected...
July 27, 2017: Pharmacology & Therapeutics
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